N-stearoyltyrosine protects primary cortical neurons against oxygen-glucose deprivation-induced apoptosis through inhibiting anandamide inactivation system

N-stearoylthrosine (NST), a synthesized anandamide (AEA) analogue, plays a neuroprotective role in neurodegenerative diseases and cerebrovascular diseases. Several studies have demonstrated that the endocannabinoids systems (ECS) are involved in the neuroprotective effects against cerebral ischemic injury. Oxygen-glucose deprivation (OGD)-induced neuronal injury elevated the levels of endocannabinoids and activated ECS. This research was conducted to investigate the neuroprotective effect of NST against OGD-induced neuronal injury in cultured primary cortical neurons and the potential mechanism involved. Cortical neurons were treated with NST at indicate concentrations for 30 min prior to injury and OGD injured neurons were incubated with normal conditions for 0-24 h. The best neuroprotective effect of NST against OGD-induced injury occurred at 10 mu M. All data indicated that the neuroprotective effect of NST against OGD-induced injury resulted from blocking anandamide membrane transporter (AMT) (IC50=11.74 nM) and inhibiting fatty acid amide hydrolase activity (FAAH) (IC50=16.54 nM). Our findings demonstrated that NST has an important role in cerebral ischemic injury pathological progression through activating cannabinoid receptors by inhibiting AEA inactivation system. These data suggested a potential role for NST in the therapeutic consideration of cerebral ischemic injury. However, inhibition of AEA inactivation system may provide a neuroprotective effect during cerebral ischemic injury. (C) 2017 Published by Elsevier Ireland Ltd.